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Influenza polymerase

Jiantao Zhang, Yanmei Hu, Christopher Foley, Yuanxiang Wang, Rami Musharrafieh, Shuting Xu, Yongtao Zhang, Chunlong Ma, Christopher Hulme, Jun Wang
Influenza viruses are respiratory pathogens that are responsible for seasonal influenza and sporadic influenza pandemic. The therapeutic efficacy of current influenza vaccines and small molecule antiviral drugs is limited due to the emergence of multidrug-resistant influenza viruses. In response to the urgent need for the next generation of influenza antivirals, we utilized a fast-track drug discovery platform by exploring multi-component reaction products for antiviral drug candidates. Specifically, molecular docking was applied to screen a small molecule library derived from the Ugi-azide four-component reaction methodology for inhibitors that target the influenza polymerase PAC -PB1N interactions...
March 15, 2018: Scientific Reports
Leen Delang, Rana Abdelnabi, Johan Neyts
Favipiravir, also known as T-705, is an antiviral drug that has been approved in 2014 in Japan to treat pandemic influenza virus infections. The drug is converted intracellularly into its active, phosphoribosylated form, which is recognized as a substrate by the viral RNA-dependent RNA polymerase. Interestingly, besides its anti-influenza virus activity, this molecule is also able to inhibit the replication of flavi-, alpha-, filo-, bunya-, arena-, noro-, and of other RNA viruses, which include neglected and (re)emerging viruses for which no antiviral therapy is currently available...
March 7, 2018: Antiviral Research
Qinhai Ma, Qingtian Yu, Xuefeng Xing, Sinian Liu, Chunyu Shi, Jiabo Luo
The San Wu Huangqin Decoction (SWHD), a traditional Chinese medicine formula, is used to treat colds caused by exposure to wind-pathogen, hyperpyrexia, infectious diseases and cancer; moreover, it is used for detoxification. The individual herbs of SWHD, such as Sophora flavescens and Scutellaria baicalensis , exhibit a wide spectrum of antiviral, anti-inflammatory, antibacterial, anticancer and other properties. The Chinese compound formula of SWHD is composed of S. flavescens, S. baicalensis and Rehmannia glutinosa ...
March 9, 2018: Viruses
Malinee Chittaganpitch, Sunthareeya Waicharoen, Thitipong Yingyong, Prabda Praphasiri, Somchai Sangkitporn, Sonja J Olsen, Kim A Lindblade
BACKGROUND: Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. OBJECTIVES: Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. METHODS: Patients with influenza-like illness (ILI; history of fever or documented temperature >38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature >38°C, cough, onset <10 days, requiring hospitalization) were enrolled from 10 sites...
March 8, 2018: Influenza and Other Respiratory Viruses
Tatiana Schäffer Gregianini, Claudete Farina Seadi, Ivone Menegolla, Letícia Garay Martins, Nilo Ikuta, Jonas Michel Wolf, Vagner Ricardo Lunge
INTRODUCTION: Infections caused by respiratory viruses are important problems worldwide, especially in children. Human metapneumovirus (hMPV) is a respiratory pathogen and causes severe infections with nonspecific symptoms. This study reports the hMPV occurrence and dissemination in southern Brazil and compares the frequency of occurrence of this virus and the human respiratory syncytial virus (hRSV) in the epidemiological weeks in a three-year period (2009-2011). METHODS: In total, 545 nasopharyngeal (NP) specimens from individuals with Severe Acute Respiratory Syndrome (SARS) who were negative for other seven respiratory viruses were analyzed for the presence of hMPV...
January 2018: Revista da Sociedade Brasileira de Medicina Tropical
Chi-Ping Chan, Chun-Kit Yuen, Pak-Hin Hinson Cheung, Sin-Yee Fung, Pak-Yin Lui, Honglin Chen, Kin-Hang Kok, Dong-Yan Jin
PACT is a double-stranded RNA-binding protein that has been implicated in host-influenza A virus (IAV) interaction. PACT facilitates the action of RIG-I in the activation of the type I IFN response, which is suppressed by the viral nonstructural protein NS1. PACT is also known to interact with the IAV RNA polymerase subunit PA. Exactly how PACT exerts its antiviral activity during IAV infection remains to be elucidated. In the current study, we demonstrated the interplay between PACT and IAV polymerase. Induction of IFN-β by the IAV RNP complex was most robust when both RIG-I and PACT were expressed...
March 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Andreas Ambrosch, Alfons Klinger, Doris Luber, Claudia Arp, Marc Lepiorz, Stefan Schroll, Frank Klawonn
There is little evidence on the clinical characteristics and the course of complicated infections with respiratory syncytial virus (RSV) compared to influenza A in adults. Therefore, the present monocenter study aims to compare infections with RSV and influenza A with regard to potential predisposing factors, clinical profile, course and outcome in hospitalized patient. MATERIAL AND METHODS:  the study was performed between Jan 1th and March 31 this year and included all hospitalized patients with a Polymerase chain-reaction-(PCR) confirmed infection of influenza A and RSV...
March 6, 2018: Deutsche Medizinische Wochenschrift
Egor P Tchesnokov, Parisa Raeisimakiani, Marianne Ngure, David Marchant, Matthias Götte
Here we report on the expression, purification and characterization of recombinant ebola virus RNA-dependent RNA polymerase (EBOV RdRp). Active protein complexes composed of the large L protein and viral protein VP35 were isolated from insect cells and analyzed using a short primer/template substrate that allowed benchmarking against related enzymes. RNA synthesis by multiprotein complexes of EBOV, influenza B, respiratory syncytial virus (RSV) and monomeric enzymes of hepatitis C and Zika (ZIKV) viruses required a 5'-phosporylated primer...
March 5, 2018: Scientific Reports
Almudena Laris González, Mónica Villa Guillén, Briseida López Martínez, Ana Estela Gamiño Arroyo, Sarbelio Moreno Espinosa, Rodolfo Jiménez Juárez, José Luis Sánchez Huerta, Daniela de la Rosa Zamboni
INTRODUCTION: Healthcare personnel (HP) are frequently exposed to influenza and can be a source of transmission to patients and other workers, resulting in high-cost outbreaks for healthcare institutions. OBJECTIVES: To analyse the presentation of HP with influenza-like illness (ILI) and the differences between individuals with influenza confirmed by polymerase chain reaction (PCR) and those with a negative test. The secondary objective was to evaluate the duration of symptomatology and work absenteeism as well as the vaccination rate of HP at a paediatric referral hospital...
March 5, 2018: Influenza and Other Respiratory Viruses
Amanda Constantinides, Ryan Gumpper, Chelsea Severin, Ming Luo
In the face of increasing drug resistance and the rapidly increasing necessity for practicality in clinical settings, drugs targeting different viral proteins are needed in order to control influenza A and B. A small molecule that tenaciously adheres to the PB2cap binding domain, part of the heterotrimeric RNA polymerase machinery of influenza A virus and influenza B virus, is a promising drug candidate. Understanding the anatomic behavior of PB2cap upon ligand binding will aid in the development of a more robust inhibitor...
March 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
Clare Wenham, Eleanor R Gray, Candice E Keane, Matthew Donati, Daniela Paolotti, Richard Pebody, Ellen Fragaszy, Rachel A McKendry, W John Edmunds
BACKGROUND: Routine influenza surveillance, based on laboratory confirmation of viral infection, often fails to estimate the true burden of influenza-like illness (ILI) in the community because those with ILI often manage their own symptoms without visiting a health professional. Internet-based surveillance can complement this traditional surveillance by measuring symptoms and health behavior of a population with minimal time delay. Flusurvey, the UK's largest crowd-sourced platform for surveillance of influenza, collects routine data on more than 6000 voluntary participants and offers real-time estimates of ILI circulation...
March 1, 2018: Journal of Medical Internet Research
Glen T Hansen, Johanna Moore, Emily Herding, Tami Gooch, Diane Hirigoyen, Kevan Hanson, Marcia Deike
BACKGROUND: Emergency Departments (ED) are challenged during influenza season by patients who present acutely during sporadic ED visits. ED management is largely empiric, often occurring without reliable diagnostics needed for targeted therapies, safe outpatient discharge, or hospital admissions. OBJECTIVE: To evaluate the impact of the influenza diagnosis on physician decision making during ED visits using the Cobas Liat® influenza A + B assay. STUDY DESIGN: Prospective study assessing the impact of rapid (<30 min), reverse-transcriptase polymerase chain reaction (RT-PCR) influenza testing on physician decision making in the ED...
February 21, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Niloofar Khalili, Ali Karimi, Mohammad-Taghi Moradi, Hedayatollah Shirzad
CONTEXT: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in addition to viral replication are due to overproduction of pro-inflammatory cytokines. Therefore, a new compound is needed to be used with current antiviral drugs to modulate overproduction of pro-inflammatory cytokines in IAV infection. OBJECTIVE: This study investigated the effect of celastrol on mRNA expression and concentration levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) that are induced by influenza A/Puerto Rico/8/34 (H1N1; PR8) in Madin-Darby Canine Kidney (MDCK) cells...
March 1, 2018: Immunopharmacology and Immunotoxicology
A V Gurov, Yu V Levina, A L Guseva, Z G Elchueva, S P Efimova, M V Gordienko
The objective of the present study was to elucidate the specific features of the clinical course of acute otitis media as well as the peculiarities of the vestibular function and the microbial paysage associated with this pathological condition under the present-day conditions. The study included 135 patients presenting with acute otitis media (AOM) at different stages of the disease. The discharge obtained from the tympanic cavity of all the patients was examined with the use of polymerase chain reaction in real time, audiological and vestibulogical methods...
2018: Vestnik Otorinolaringologii
Jeong-Min Kim, Hee-Dong Jung, Hyang-Min Cheong, Anna Lee, Nam-Joo Lee, Hyuk Chu, Sung Soon Kim, Jang-Hoon Choi
The prevalence of eight respiratory viruses detected in patients with acute respiratory infections (ARIs) in Korea was investigated through analysis of data recorded by the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) from 2013 to 2015. Nasal aspirate and throat swabs specimens were collected from 36,915 patients with ARIs, and viral nucleic acids were detected by real-time (reverse-transcription) polymerase chain reaction for eight respiratory viruses, including human respiratory syncytial viruses (HRSVs), influenza viruses (IFVs), human parainfluenza viruses (HPIVs), human coronaviruses (HCoVs), human rhinovirus (HRV), human adenovirus (HAdV), human bocavirus (HBoV), and human metapneumovirus (HMPV)...
February 28, 2018: Journal of Medical Virology
Reyaz A Para, Bashir A Fomda, Rafi A Jan, Sonaullah Shah, Parvaiz A Koul
Background: There is a paucity of literature regarding the microbial etiology of community-acquired pneumonia (CAP) in India. The current study was aimed to study the microbial etiology of hospitalized adults with CAP. Methods: The study was conducted in a 700-bedded North Indian hospital. Consecutive adults admitted with CAP over a period of 2 years from 2013 to 2015 were recruited for the study, and apart from clinical evaluation underwent various microbiological studies in the form of blood culture, sputum culture, urinary antigen for pneumococcus and Legionella, serology for Mycoplasma and Chlamydia and real-time reverse transcriptase polymerase chain reaction for influenza viruses...
March 2018: Lung India: Official Organ of Indian Chest Society
Zhihao Zhuo, Jin Wang, Wendi Chen, Xiaosong Su, Mengyuan Chen, Mujin Fang, Shuizhen He, Shiyin Zhang, Shengxiang Ge, Jun Zhang, Ningshao Xia
BACKGROUND: Morbidity and mortality from influenza A (Flu A) have increased in recent years. Timely diagnosis and management are critical for disease control. Therefore, the development of a rapid, accurate, and portable analytical method for on-site analysis is imperative. OBJECTIVES: The aim of this work was to develop a rapid, on-site, automated assay for the detection of Flu A and to evaluate the assay. METHODS: A handheld instrument (TD-01) based on capillary convective polymerase chain reaction (PCR) was developed for rapid on-site detection of Flu A...
February 22, 2018: Molecular Diagnosis & Therapy
Dieng Assane, Camara Makhtar, Diop Abdoulaye, Fall Amary, Boiro Djibril, Diop Amadou, Diouf Jean Baptiste Niokhor, Diop Amadou, Loucoubar Cheikh, Dia Ndongo, Niang Mbayame, Fall Lamine, Boye Cheikh Saad Bouh
Acute respiratory infections (ARIs) are the leading cause of infectious disease-related morbidity, hospitalization, and morbidity among children worldwide. This study aimed to assess the viral and bacterial causes of ARI morbidity and mortality in children under 5 years in Senegal. Nasopharyngeal samples were collected from children under 5 years who had ARI. Viruses and bacteria were identified using multiplex real-time reverse transcription-polymerase chain reaction and conventional biochemical techniques, respectively...
2018: Microbiology Insights
Zizhang Sheng, Runxia Liu, Jieshi Yu, Zhiguang Ran, Simon J Newkirk, Wenfeng An, Feng Li, Dan Wang
Influenza B virus (FLUBV) is an important pathogen that infects humans and causes seasonal influenza epidemics. To date, little is known about defective genomes of FLUBV and their roles in viral replication. In this study, by using a next-generation sequencing approach, we analyzed total mRNAs extracted from A549 cells infected with B/Brisbane/60/2008 virus (Victoria lineage), and identified four defective FLUBV genomes with two (PB1∆A and PB1∆B) from the polymerase basic subunit 1 (PB1) segment and the other two (M∆A and M∆B) from the matrix (M) protein-encoding segment...
February 12, 2018: Journal of General Virology
Mohsen Meidani, Seyed Alireza Mirmohammad Sadeghi
Background: Respiratory infections are a frequent cause of fever in neutropenic patients, whereas respiratory viral infections are not frequently considered as a diagnosis, which causes high morbidity and mortality in these patients. Materials and Methods: This prospective study was performed on 36 patients with neutropenia who admitted to hospital were eligible for inclusion with fever (single temperature of >38.3°C or a sustained temperature of >38°C for more than 1 h), upper and lower respiratory symptoms...
2018: Advanced Biomedical Research
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